Prefoldin chaperones are involved in numerous protein binding functions including protein fold

Not all L1 muscle cells do respond to GABA application, nor do they show GFP-label associated to GABA receptors, in agreement with the fact that at the L1 stage GABA receptors are expressed only in body ventral muscles and not in body dorsal muscles. Thus, our study gives further evidence that the L1 cell culture reproduces the in vivo situation. Overall responses of GABA receptors to anthelmintic drugs were evaluated by measuring macroscopic currents from L1 muscle cells in the whole-cell configuration. Unfortunately, these cultured muscle cells are not technically suitable for successive drug applications and they therefore do not allow complete pharmacological assays. This relatively limited information is nevertheless still valuable when complemented with single-channel recordings and behavioral assays. Macroscopic currents elicited by GABA show rapid onset as well as rapid and full decay under the sustained pulse of agonist, indicating full desensitization. Cardiomyocytes are maintained by intricate molecular regulatory programs that involve a multitude of transcription factors. Heart development utilises conserved transcription factor families such as GATA, Nk2, HAND, MEF2 and TBX as the central hub of regulation. Interestingly reactivation of some of these developmental regulators such as GATA factors is crucial to promoting the cardiac hypertrophy disease state suggesting functional activity is maintained into adulthood. GATA-4, a well-known enhancer of cardiac development has an indispensable functional interaction with FOG-2. FOG-2 and GATA-4 are co-expressed in both the developing and adult heart and FOG-2 regulates GATA-4 transcriptional activity on cardiac specific genes atrial natriuretic peptide, b-type natriuretic peptide and alpha myosin heavy chain. FOG-2 deficient murine embryos have severe cardiac malformations resulting in embryonic lethality and this phenotype is recapitulated to a large extent in transgenic GATA-4 embryos that have a knock-in mutation that prevents a GATA-4/ FOG-2 interaction. Similarly, FOG-2 polymorphisms are associated with the congenital heart disease Tetralogy of Fallot revealing conserved FOG-2 function in human heart development. In addition to their role in development, GATA-4 and FOG-2 have functional roles in regulation of the adult heart, both shown to participate in the regulation of cardiac hypertrophy. Given the importance of FOG-2 in cardiomyocyte biology as a GATA-4 cofactor, we hypothesised that FOG-2 may bridge other novel transcription factors into the cardiac regulatory network as a protein cofactor. Art27 has a high capacity to physically interact with other proteins. In this study it was found to physically associate with FOG-2, GATA-4, GATA-6, GATA-1 and Nkx2.5. In agreement, previous studies also observed that Art27 is frequently involved in protein interactions. Art27 has high homology to the prefoldin family of molecular chaperones.

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